This study investigated the mechanism of Chaishao Kaiyu Decoction in improving hippocampal neuroinflammation in depressed rats based on complement component 3(C3)/C3 receptor(C3aR). A total of 60 SD rats were randomly divided into a blank group, a model group, high, medium, and low dose groups of Chaishao Kaiyu Decoction, and a positive drug group, with 10 rats in each group. Except for the blank group, chronic unpredictable mild stress(CUMS) was used to construct depression models in other groups. Sucrose preference, open-field experiment, forced swimming, and water maze were used to detect the changes in depression-like behavior in each group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum inflammatory factor level in rats, and hematoxylin-eosin(HE) staining and Nissl staining were employed to observe the pathological damage of hippocampal neurons. Golgi-Cox staining was used to observe the dendritic spine damage of hippocampal neurons, and immunofluorescence and Western blot were utilized to detect the expression of microglial marker Iba-1 and C3/C3aR protein in the hippocampus of rats. The behavioral results showed that compared with the model group, Chaishao Kaiyu Decoction could significantly strengthen the sugar water preference, increase the distance and number of voluntary activities, shorten the immobility time in forced swimming and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant. ELISA results showed that the content of inflammatory factors in the hippocampus of depressed rats was significantly higher than that of the blank group, and the content of inflammatory factors decreased significantly after the intervention of Chaishao Kaiyu Decoction. In addition, Chaishao Kaiyu Decoction could relieve pathological damage such as cell swelling and loose arrangement of hippocampus tissue. In the Western blot experiment, the expression levels of C3 and C3aR proteins in the model group were higher than those in the blank group, while the expression of C3 and C3aR in Chaishao Kaiyu Decoction could be down-regulated. Immunofluorescence results showed that compared with the model group, the fluorescence intensity of microglia marker Iba-1 decreased significantly after the intervention of Chaishao Kaiyu Decoction and positive drugs. The antidepressant effect of Chaishao Kaiyu Decoction may be related to the down-regulation of C3/C3aR signaling pathway-related proteins, thus alleviating hippocampal inflammation.
Animals ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Male ; Depression/metabolism* ; Complement C3/metabolism* ; Receptors, Complement/metabolism* ; Humans ; Neuroinflammatory Diseases/genetics*

OBJECTIVE: To explore the relationship between serum complement levels at diagnosis and prognosis in patients with aggressive non-Hodgkin lymphoma(NHL). METHODS: The clinical data of 102 patients with aggressive non-Hodgkin lymphoma diagnosed in the First Hospital of Lanzhou University from February 2017 to March 2023 were selected to analyze the correlation between serum complement C3 and C4 levels and prognosis of patients with aggressive NHL at the time of initial diagnosis. The optimal cut-off point of C3 and C4 were obtained by calculating the Jorden index through the receiver operating characteristic（ROC） curve, and 102 patients were divided into low C3 group (C3< 1.07) and high C3 group (C3≥1.07), low C4 group (C4< 0.255) and high C4 group (C4≥0.255). The effects of serum C3 and C4 levels on the prognosis of these patients were analyzed. RESULTS: ROC curve analysis showed that the area under the curve (AUC) of C3 and C4 in predicting the prognosis of aggressive NHL patients was 0.634 (95%CI ：0.525-0.743；P =0.025) and 0.651 (95%CI ：0.541-0.761；P =0.012), respectively. The optimal cut-off points for C3 and C4 were 1.07 and 0.255, respectively. K-M survival analysis showed that groups with high C3 and C4 levels had shorter progression-free survival (PFS) (P =0.0079; P =0.0092) and overall survival (OS) (P =0.021; P =0.021). Multivariate Cox analysis showed that high level serum complement C3 (HR=2.37, 95%CI : 1.07-5.24, P =0.034) and age ≥60 years (HR=2.34, 95%CI : 1.11-4.95, P =0.025) were independent risk factors for PFS in patients with aggressive NHL. High level complement C3 (HR=2.37, 95%CI : 1.09-5.13, P =0.029) and age ≥60 years at diagnosis (HR=2.40, 95%CI : 1.13-5.13, P =0.024) were independent risk factors for OS in patients with aggressive NHL. CONCLUSION The level of serum complement C3 at diagnosis is one of the prognostic factors in patients with aggressive NHL.
Humans ; Lymphoma, Non-Hodgkin/blood* ; Prognosis ; Complement C3/metabolism* ; Complement C4/metabolism* ; ROC Curve ; Male ; Female ; Middle Aged ; Adult ; Aged

Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*

Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

OBJECTIVE: To stratify systemic lupus erythematosus (SLE) patients clinically, to analyze the clinical characteristics of patients with and without disease activity, and to explore the application va-lue of key clinical indicators in assessing disease activity, as well as to construct an evaluation model. METHODS: A retrospective analysis was conducted on clinical data of the SLE patients diagnosed at Peking University People' s Hospital from May 1995 to April 2014. Demographic information, clinical manifestations, laboratory tests, and antibody detection results were collected. The patients were divided into active and inactive groups based on systemic lupus erythematosus disease activity index 2000(SLEDAI-2000)scores. t-tests, Mann-Whitney U tests, and χ² tests were used to compare the differences between the groups. Spearman correlation analysis was used to evaluate the relevant clinical indicators associated with SLE activity in the active disease group. Based on the results of statistical analysis, a Logistic regression model was constructed, and the performance of the model was evaluated. RESULTS: No significant differences were found in demographic characteristics between the two groups. In the active disease group, positive rates of antinuclear antibodies (ANA) and anti-double-stranded DNA antibodies (anti-dsDNA) were increased; white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), lymphocytes (LY), total protein (TP), albumin (ALB), and complement 3(C3) levels were significantly decreased; while immunoglobulin A and G levels were markedly elevated. The correlation analysis results showed that hemoglobin, albumin, C3, and complement 4(C4) had higher correlation indices compared with other clinical indicators. Among these, C3 exhibited a certain negative correlation with disease activity. The Logistic regression model based on 12 significantly different indicators (P < 0.05) achieved an accuracy of 91.4%, sensitivity of 94.4%, specificity of 81.0%, and the area under curve (AUC) of the receiver operating characteristic (ROC) was 0.944. CONCLUSION This study comprehensively evaluated a range of clinical indicators related to SLE disease activity, providing a thorough understanding of both laboratory and clinical markers. The Logistic regression model, which was primarily constructed using laboratory test indicators, such as inflammatory markers, immune response parameters, and organ involvement metrics, demonstrated a high degree of accuracy in assessing the disease activity in SLE patients. Consequently, this model might provide a new basis for the diagnosis and treatment of SLE patients, offering significant clinical diagnostic value.
Humans ; Lupus Erythematosus, Systemic/diagnosis* ; Retrospective Studies ; Antibodies, Antinuclear/blood* ; Complement C3/metabolism* ; Complement C4/metabolism* ; Logistic Models ; Severity of Illness Index ; Leukocyte Count ; Female ; Male ; Serum Albumin/analysis*

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Animals ; Astrocytes/metabolism* ; Complement C3/metabolism* ; Epilepsy ; Mice ; Neurons/pathology* ; Status Epilepticus ; TRPV Cation Channels/metabolism*

OBJECTIVE: To investigate the significance of detecting serum complement C3 and C4 in patients with multiple myeloma (MM) and to explore its correlation with myeloma bone disease (MBD). METHODS: The levels of serum complement C3 and C4 in 69 MM patients and 30 healthy people were examined by scatter nephelometry. The bone density of L1-4 vertebral body, bilateral femoral neck and bilateral hip joints were measured by dual energy bone density meter (DXA). RESULTS: The levels of serum complement C3 and C4 in MM patients significantly increased in comparison with that in healthy people (P＜0.01). The patients in advanced clinical stage exhibited a higher levels of C3 and C4 than those in stable stage (P＜0.01). In addition, the patients with grade C of MBD had a higher levels of serum complement C3 and C4 than those in patients with grade A and B of MBD (P＜0.01). The levels of serum complement C3 and C4 in MM patients negatively correlated with bone density in L1-4 vertebral body, bilateral femoral necks and hip joints. The correlation coefficients were r=-0.938, r=-0.659, r=-0.745, r=-0.748, r=-0.596 in complement C3 and r=-0.908, r=-0.623, r=-0.710, r=-0.714, r=-0.595 in complement C4, respectively. CONCLUSION The levels of complement C3 and C4 positively correlate with the severity of bone disease and bone density in MM patients, which suggests that complement C3 and C4 plays important roles in the development of MBD. The levels of serum C3 and C4 may be the sensitive biomarkers of MBD.
Biomarkers ; Complement C3 ; metabolism ; Complement C4 ; metabolism ; Femur Neck ; Humans ; Multiple Myeloma

OBJECTIVETo investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients.

METHODSFifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores.

RESULTSNo significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05).

CONCLUSIONNutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

C-Reactive Protein ; metabolism ; Complement C3 ; metabolism ; Humans ; Hydrocortisone ; blood ; Nutritional Status ; Prealbumin ; metabolism ; Prognosis ; Severity of Illness Index ; Stroke ; diagnosis ; physiopathology

OBJECTIVETo explore lupus nephritis (LN) patients' monocyte chemotactic protein 1 (MCP-1) and urinary IP-10 (ulP-10) levels, the correlation between each clinical activity index and rheumatism syndrome, thereby proving objective evidence for microscopic typing of rheumatism syndrome.

METHODSTotally 60 LN patients were assigned to the rheumatism group (31 cases) and the non-rheumatism group (29 cases). Besides, 20 healthy volunteers were recruited as the normal control group. Clinical data and renal pathology were collected, and urinary levels of MCP-1 and IP-10 detected by ELISA. The correlation between rheumatism syndrome and each activity index as well as manifestations of clinical activities was comprehensively analyzed. Results (1) Patients in the rheumatism group were more liable to occur fever, serositis, edema, and hypertension (P<0.05). (2) Compared with the non-rheumatism group, patients in the rheumatism group exhibited much higher levels of 24 h protein quantification and blood urea nitrogen, higher levels of uMCP-1 and ulP-10. Microscopic hematuria, anti-ds-DNA, anti-Sm, the positive rate of AnuA, scores of SLEDAI and BILAG were higher in the rheumatism group than in the non-rheumatism group (P<0.05). Levels of plasma albumin and complement C3 were lower in the rheumatism group than in the non-rheumatism group (P<0.05). (3) The average activity index (AI) of the renal pathology was higher in the rheumatism group than in the non-rheumatism group. The most frequent pathological type of rheumatism group was type IV of LN.

CONCLUSIONSMore severe renal damage and immune abnormality occurred in LN patients of rheumatism syndrome. Rheumatism syndrome is closely correlated to clinical activity indices.

Biomedical Research ; Chemokine CCL2 ; metabolism ; Complement C3 ; metabolism ; Hematuria ; Humans ; Kidney ; Lupus Nephritis ; epidemiology ; metabolism ; Rheumatic Diseases ; epidemiology ; metabolism

OBJECTIVETo explore the effect of lappaconitine on patient-controlled intravenous analgesia (PCIA) and serum complement 3 and 4 (C3 and C4) levels of cancer patients undergoing rectum surgery.

METHODSTotally 60 patients, who were scheduled for rectum carcinoma surgery, were recruited to the study and assigned in 3 groups, the blank control group, the tramadol group, and the lappaconitine group, 20 in each group. Lappaconitine (8 mg) was intravenously dripped to patients in the lappaconitine group 30 min before ending the operation. PCIA started as soon as the end of the surgery and the total dose of lappaconitine was 36 mg. Patients of the tramadol group were treated with tramadol (100 mg) intravenously within 30 min before ending the operation. The dripping was completed within 30 min. PCIA was started as soon as the end of the surgery and the total dose of lappaconitine was 36 mg. Tramadol (100 mg) was intravenously dripped to patients in the tramadol group 30 min before ending the operation. PICA was started as soon as the end of the surgery and the total dose of tramadol was 900 mg. Pethidine (50 mg) and droperidol (2. 5 mg) was intramuscularly injected to patients in the blank control group for pain relief according to their complaints. Pain degrees were assessed by visual analog scale (VAS) 12 h before surgery, 12, 24, 48, and 72 h after surgery. Blood samples were withdrawn at the same time point. Contents of serum C3 and C4 were determined by immunoturbidimetry.

RESULTSVAS scores of the blank control group were significantly higher after surgery than before surgery (P <0. 01). There was no statistical difference in VAS scores between before surgery and after surgery in the tramadol group and the lappaconitine group (P >0. 05). VAS scores were significantly lower at each post-surgery time point in the tramadol group and the lappaconitine group than in the blank control group with statistical difference (P < 0.01). There was no statistical difference in VAS scores at each post-surgery time point between the tramadol group and the lappaconitine group (P >0. 05). Compared with before surgery, contents of serum C3 and C4 significantly decreased in all of the three groups at 12, 24, and 48 h after surgery (P < 0.05, P < 0.01). They recovered to the pre-surgery level till 72 h after surgery (P > 0.05). Serum C3 and C4 contents at 48 h after surgery were higher in the tramadol group than in the blank control group (P < 0.05). Serum C3 and C4 contents at 24 and 48 h after surgery were higher in the lappaconitine group than in the blank control group (P < 0.05). There was no statistical difference in serum C3 and C4 contents at each time point between the tramadol group and the lappaconitine group (P > 0.05). VAS scores were obviously negatively correlated with serum contents of C3 and C4 (r = -0.622, r = -0.649, P < 0.01).

CONCLUSIONSLappaconitine (used at the dose in this study) showed better pain relief effect after surgery. Besides, it could inhibit the surgic wound and pain, and elevate serum contents of C3 and C4.

Aconitine ; analogs & derivatives ; therapeutic use ; Analgesia, Patient-Controlled ; methods ; Analgesics, Non-Narcotic ; therapeutic use ; Complement C3 ; metabolism ; Digestive System Surgical Procedures ; Humans ; Neoplasms ; Orthopedic Procedures ; Pain Measurement ; Pain, Postoperative ; Postoperative Period ; Rectum ; surgery ; Tramadol